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DRd improves PFS in transplant-ineligible MM
SAN DIEGO—An interim analysis from the MAIA trial showed that adding daratumumab to lenalidomide and dexamethasone could significantly improve progression-free survival (PFS) in older patients with multiple myeloma (MM) who were ineligible for transplant.
The 30-month PFS rate was 71% in patients who received daratumumab plus lenalidomide and dexamethasone (DRd) and 56% in patients who received only lenalidomide and dexamethasone (Rd).
“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” said Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille in France.
Dr. Facon presented results from MAIA during the late-breaking abstracts session at the 2018 ASH Annual Meeting (abstract LBA-2).
The phase 3 trial (NCT02252172) enrolled 737 transplant-ineligible patients with newly diagnosed MM.
The patients were randomly assigned to DRd or Rd. Daratumumab was given at 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression.
Lenalidomide was given at 25 mg orally per day on days 1-21 until disease progression, and dexamethasone was given at 40 mg orally or intravenously weekly until disease progression.
The median patient age was 73 years, and 99% of all patients were 65 or older. Demographic and clinical characteristics were well balanced between the treatment arms.
Results
The primary endpoint of PFS was superior with DRd.
At a median follow-up of 28 months, the median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm.
The 30-month PFS rate was 71% in the DRd arm and 56% in the Rd arm (hazard ratio [HR]=0.56; P<0.0001).
DRd was associated with a significantly higher overall response rate than Rd—93% and 81%, respectively (P<0.0001).
The complete response rates were 48% and 25%, respectively (P<0.0001). The rates of very good partial response or better were 79% and 53%, respectively (P<0.0001). And the rates of minimal residual disease negativity were 24% and 7%, respectively (P<0.0001).
DRd was associated with infusion-related reactions in 41% of patients, and 3% were grade 3 or 4 in severity.
Hematologic treatment-emergent adverse events of grade 3 or higher that were more common with DRd than Rd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%).
Conversely, grade 3/4 thrombocytopenia (7% vs. 9%) and anemia (12% vs. 20%) were more frequent with Rd.
Nonhematologic treatment-emergent adverse events that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia.
Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the treatment arms.
Janssen funded this study. Dr. Facon reported relationships with Celgene, Janssen, Takeda, Sanofi, Amgen, Karyopharm, and Oncopeptides.
SAN DIEGO—An interim analysis from the MAIA trial showed that adding daratumumab to lenalidomide and dexamethasone could significantly improve progression-free survival (PFS) in older patients with multiple myeloma (MM) who were ineligible for transplant.
The 30-month PFS rate was 71% in patients who received daratumumab plus lenalidomide and dexamethasone (DRd) and 56% in patients who received only lenalidomide and dexamethasone (Rd).
“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” said Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille in France.
Dr. Facon presented results from MAIA during the late-breaking abstracts session at the 2018 ASH Annual Meeting (abstract LBA-2).
The phase 3 trial (NCT02252172) enrolled 737 transplant-ineligible patients with newly diagnosed MM.
The patients were randomly assigned to DRd or Rd. Daratumumab was given at 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression.
Lenalidomide was given at 25 mg orally per day on days 1-21 until disease progression, and dexamethasone was given at 40 mg orally or intravenously weekly until disease progression.
The median patient age was 73 years, and 99% of all patients were 65 or older. Demographic and clinical characteristics were well balanced between the treatment arms.
Results
The primary endpoint of PFS was superior with DRd.
At a median follow-up of 28 months, the median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm.
The 30-month PFS rate was 71% in the DRd arm and 56% in the Rd arm (hazard ratio [HR]=0.56; P<0.0001).
DRd was associated with a significantly higher overall response rate than Rd—93% and 81%, respectively (P<0.0001).
The complete response rates were 48% and 25%, respectively (P<0.0001). The rates of very good partial response or better were 79% and 53%, respectively (P<0.0001). And the rates of minimal residual disease negativity were 24% and 7%, respectively (P<0.0001).
DRd was associated with infusion-related reactions in 41% of patients, and 3% were grade 3 or 4 in severity.
Hematologic treatment-emergent adverse events of grade 3 or higher that were more common with DRd than Rd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%).
Conversely, grade 3/4 thrombocytopenia (7% vs. 9%) and anemia (12% vs. 20%) were more frequent with Rd.
Nonhematologic treatment-emergent adverse events that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia.
Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the treatment arms.
Janssen funded this study. Dr. Facon reported relationships with Celgene, Janssen, Takeda, Sanofi, Amgen, Karyopharm, and Oncopeptides.
SAN DIEGO—An interim analysis from the MAIA trial showed that adding daratumumab to lenalidomide and dexamethasone could significantly improve progression-free survival (PFS) in older patients with multiple myeloma (MM) who were ineligible for transplant.
The 30-month PFS rate was 71% in patients who received daratumumab plus lenalidomide and dexamethasone (DRd) and 56% in patients who received only lenalidomide and dexamethasone (Rd).
“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” said Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille in France.
Dr. Facon presented results from MAIA during the late-breaking abstracts session at the 2018 ASH Annual Meeting (abstract LBA-2).
The phase 3 trial (NCT02252172) enrolled 737 transplant-ineligible patients with newly diagnosed MM.
The patients were randomly assigned to DRd or Rd. Daratumumab was given at 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression.
Lenalidomide was given at 25 mg orally per day on days 1-21 until disease progression, and dexamethasone was given at 40 mg orally or intravenously weekly until disease progression.
The median patient age was 73 years, and 99% of all patients were 65 or older. Demographic and clinical characteristics were well balanced between the treatment arms.
Results
The primary endpoint of PFS was superior with DRd.
At a median follow-up of 28 months, the median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm.
The 30-month PFS rate was 71% in the DRd arm and 56% in the Rd arm (hazard ratio [HR]=0.56; P<0.0001).
DRd was associated with a significantly higher overall response rate than Rd—93% and 81%, respectively (P<0.0001).
The complete response rates were 48% and 25%, respectively (P<0.0001). The rates of very good partial response or better were 79% and 53%, respectively (P<0.0001). And the rates of minimal residual disease negativity were 24% and 7%, respectively (P<0.0001).
DRd was associated with infusion-related reactions in 41% of patients, and 3% were grade 3 or 4 in severity.
Hematologic treatment-emergent adverse events of grade 3 or higher that were more common with DRd than Rd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%).
Conversely, grade 3/4 thrombocytopenia (7% vs. 9%) and anemia (12% vs. 20%) were more frequent with Rd.
Nonhematologic treatment-emergent adverse events that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia.
Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the treatment arms.
Janssen funded this study. Dr. Facon reported relationships with Celgene, Janssen, Takeda, Sanofi, Amgen, Karyopharm, and Oncopeptides.
Frailty-adjusted treatment strategy emerges in myeloma
SAN DIEGO – Switching to lenalidomide maintenance after nine cycles of lenalidomide/dexamethasone (Rd) may avoid toxicity without sacrificing survival benefit in elderly multiple myeloma patients of intermediate fitness, results from a randomized trial showed.
The Rd-R strategy yielded a “slight improvement” in event-free survival due largely to fewer adverse events, and no significant differences in progression-free or overall survival versus continuous Rd, reported Alessandra Larocca, MD, of GIMEMA/European Myeloma Network in Italy.
That finding suggests the promise of adapting myeloma treatment to a patient’s level of frailty or fitness, as determined by a myeloma frailty score, Dr. Larocca said at the annual meeting of the American Society of Hematology.
“A frailty-adjusted treatment approach is important in intermediate-fit patients to balance efficacy and safety,” she said.
The frailty score, developed by the International Myeloma Working Group (IMWG), classifies individuals as fit, intermediate, or frail based on age, comorbidities, cognitive status, and functional status. In a 2015 report in Blood, the IMWG frailty score was shown to predict mortality and treatment-related toxicity in elderly myeloma patients.
Dr. Larocca described results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed myeloma patients of intermediate fitness and randomized them to continuous Rd or nine cycles of Rd induction followed by lenalidomide maintenance (Rd-R).
The goal was to see if Rd could be “further optimized” for elderly, intermediate-fit patients, Dr. Larocca said.
The primary endpoint of RV-MM-PI-0752 was event-free survival, which included grade 4 hematologic and grade 3-4 nonhematologic adverse events, lenalidomide discontinuation, disease progression, or death.
Median event-free survival was 9.3 months for the Rd-R strategy, compared with 6.6 months for continuous Rd (hazard ratio, 0.72; 95% confidence interval, 0.52-0.99; P = .044), Dr. Larocca reported.
No difference was seen in survival outcomes, she added. The 20-month progression-free survival was 43% and 42% for Rd-R and continuous Rd, respectively. The 20-month overall survival was 84% vs. 79%, with P values that were not significant for either comparison.
Patients in the Rd-R group had a somewhat higher incidence of grade 3 or greater neutropenia, but the continuous Rd group had a somewhat higher rate of nonhematologic adverse events, leading to slightly higher rates of lenalidomide discontinuation and dose reduction, Dr. Larocca said.
Overall, 9% of patients dropped out of the RV-MM-PI-0752 trial within the first 60 days, due mainly to toxicity, she added.
“We have to evaluate how to better prevent toxicity, potentially enabling patients to stay on therapy longer,” Dr. Larocca said. “Probably we have to evaluate, in prospective clinical trials, the role of up-front dose adjustment or dose reduction, and subsequent dose increase in a subgroup of patients.”
Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.
SOURCE: Larocca A, et al. ASH 2018, Abstract 305.
SAN DIEGO – Switching to lenalidomide maintenance after nine cycles of lenalidomide/dexamethasone (Rd) may avoid toxicity without sacrificing survival benefit in elderly multiple myeloma patients of intermediate fitness, results from a randomized trial showed.
The Rd-R strategy yielded a “slight improvement” in event-free survival due largely to fewer adverse events, and no significant differences in progression-free or overall survival versus continuous Rd, reported Alessandra Larocca, MD, of GIMEMA/European Myeloma Network in Italy.
That finding suggests the promise of adapting myeloma treatment to a patient’s level of frailty or fitness, as determined by a myeloma frailty score, Dr. Larocca said at the annual meeting of the American Society of Hematology.
“A frailty-adjusted treatment approach is important in intermediate-fit patients to balance efficacy and safety,” she said.
The frailty score, developed by the International Myeloma Working Group (IMWG), classifies individuals as fit, intermediate, or frail based on age, comorbidities, cognitive status, and functional status. In a 2015 report in Blood, the IMWG frailty score was shown to predict mortality and treatment-related toxicity in elderly myeloma patients.
Dr. Larocca described results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed myeloma patients of intermediate fitness and randomized them to continuous Rd or nine cycles of Rd induction followed by lenalidomide maintenance (Rd-R).
The goal was to see if Rd could be “further optimized” for elderly, intermediate-fit patients, Dr. Larocca said.
The primary endpoint of RV-MM-PI-0752 was event-free survival, which included grade 4 hematologic and grade 3-4 nonhematologic adverse events, lenalidomide discontinuation, disease progression, or death.
Median event-free survival was 9.3 months for the Rd-R strategy, compared with 6.6 months for continuous Rd (hazard ratio, 0.72; 95% confidence interval, 0.52-0.99; P = .044), Dr. Larocca reported.
No difference was seen in survival outcomes, she added. The 20-month progression-free survival was 43% and 42% for Rd-R and continuous Rd, respectively. The 20-month overall survival was 84% vs. 79%, with P values that were not significant for either comparison.
Patients in the Rd-R group had a somewhat higher incidence of grade 3 or greater neutropenia, but the continuous Rd group had a somewhat higher rate of nonhematologic adverse events, leading to slightly higher rates of lenalidomide discontinuation and dose reduction, Dr. Larocca said.
Overall, 9% of patients dropped out of the RV-MM-PI-0752 trial within the first 60 days, due mainly to toxicity, she added.
“We have to evaluate how to better prevent toxicity, potentially enabling patients to stay on therapy longer,” Dr. Larocca said. “Probably we have to evaluate, in prospective clinical trials, the role of up-front dose adjustment or dose reduction, and subsequent dose increase in a subgroup of patients.”
Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.
SOURCE: Larocca A, et al. ASH 2018, Abstract 305.
SAN DIEGO – Switching to lenalidomide maintenance after nine cycles of lenalidomide/dexamethasone (Rd) may avoid toxicity without sacrificing survival benefit in elderly multiple myeloma patients of intermediate fitness, results from a randomized trial showed.
The Rd-R strategy yielded a “slight improvement” in event-free survival due largely to fewer adverse events, and no significant differences in progression-free or overall survival versus continuous Rd, reported Alessandra Larocca, MD, of GIMEMA/European Myeloma Network in Italy.
That finding suggests the promise of adapting myeloma treatment to a patient’s level of frailty or fitness, as determined by a myeloma frailty score, Dr. Larocca said at the annual meeting of the American Society of Hematology.
“A frailty-adjusted treatment approach is important in intermediate-fit patients to balance efficacy and safety,” she said.
The frailty score, developed by the International Myeloma Working Group (IMWG), classifies individuals as fit, intermediate, or frail based on age, comorbidities, cognitive status, and functional status. In a 2015 report in Blood, the IMWG frailty score was shown to predict mortality and treatment-related toxicity in elderly myeloma patients.
Dr. Larocca described results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed myeloma patients of intermediate fitness and randomized them to continuous Rd or nine cycles of Rd induction followed by lenalidomide maintenance (Rd-R).
The goal was to see if Rd could be “further optimized” for elderly, intermediate-fit patients, Dr. Larocca said.
The primary endpoint of RV-MM-PI-0752 was event-free survival, which included grade 4 hematologic and grade 3-4 nonhematologic adverse events, lenalidomide discontinuation, disease progression, or death.
Median event-free survival was 9.3 months for the Rd-R strategy, compared with 6.6 months for continuous Rd (hazard ratio, 0.72; 95% confidence interval, 0.52-0.99; P = .044), Dr. Larocca reported.
No difference was seen in survival outcomes, she added. The 20-month progression-free survival was 43% and 42% for Rd-R and continuous Rd, respectively. The 20-month overall survival was 84% vs. 79%, with P values that were not significant for either comparison.
Patients in the Rd-R group had a somewhat higher incidence of grade 3 or greater neutropenia, but the continuous Rd group had a somewhat higher rate of nonhematologic adverse events, leading to slightly higher rates of lenalidomide discontinuation and dose reduction, Dr. Larocca said.
Overall, 9% of patients dropped out of the RV-MM-PI-0752 trial within the first 60 days, due mainly to toxicity, she added.
“We have to evaluate how to better prevent toxicity, potentially enabling patients to stay on therapy longer,” Dr. Larocca said. “Probably we have to evaluate, in prospective clinical trials, the role of up-front dose adjustment or dose reduction, and subsequent dose increase in a subgroup of patients.”
Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.
SOURCE: Larocca A, et al. ASH 2018, Abstract 305.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: Median event-free survival was 9.3 months for the Rd induction followed by lenalidomide maintenance, compared with 6.6 months for continuous Rd (P = .044).
Study details: Results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed multiple myeloma patients of intermediate fitness.
Disclosures: Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.
Source: Larocca A et al. ASH 2018, Abstract 305.
Health Canada approves new indication for daratumumab
Health Canada has approved a third indication for daratumumab (Darzalex®) in multiple myeloma (MM).
The drug is now approved for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed MM who are ineligible for autologous stem cell transplant.
Health Canada previously approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least one prior therapy.
Health Canada also approved daratumumab as monotherapy for MM patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent.
For the product monograph and more information about daratumumab, visit https://www.janssen.com/canada/products.
Trial results
Health Canada’s latest approval of daratumumab is supported by data from the phase 3 ALCYONE study (NCT02195479), which were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.
ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).
The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.
The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.
The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).
Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.
The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.
The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).
The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.
The ALCYONE trial was sponsored by Janssen Research & Development, LLC.
Health Canada has approved a third indication for daratumumab (Darzalex®) in multiple myeloma (MM).
The drug is now approved for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed MM who are ineligible for autologous stem cell transplant.
Health Canada previously approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least one prior therapy.
Health Canada also approved daratumumab as monotherapy for MM patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent.
For the product monograph and more information about daratumumab, visit https://www.janssen.com/canada/products.
Trial results
Health Canada’s latest approval of daratumumab is supported by data from the phase 3 ALCYONE study (NCT02195479), which were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.
ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).
The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.
The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.
The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).
Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.
The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.
The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).
The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.
The ALCYONE trial was sponsored by Janssen Research & Development, LLC.
Health Canada has approved a third indication for daratumumab (Darzalex®) in multiple myeloma (MM).
The drug is now approved for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed MM who are ineligible for autologous stem cell transplant.
Health Canada previously approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least one prior therapy.
Health Canada also approved daratumumab as monotherapy for MM patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent.
For the product monograph and more information about daratumumab, visit https://www.janssen.com/canada/products.
Trial results
Health Canada’s latest approval of daratumumab is supported by data from the phase 3 ALCYONE study (NCT02195479), which were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.
ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).
The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.
The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.
The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).
Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.
The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.
The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).
The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.
The ALCYONE trial was sponsored by Janssen Research & Development, LLC.
10 Important VA Studies You Might Have Missed at ASH
With hundreds of sessions and thousands of abstracts, it can be difficult to wade through all the new findings to find the most significant and relevant findings. Federal Practitioner consulted with Association of VA Hematology/Oncology members who attended the meeting, VA researchers, and other sources to provide these nuggets you might have missed on lymphomas, white blood cells, leukemias, and multiple myeloma:
Lymphomas
This retrospective analysis of diffuse large B cell lymphoma (DCBL) patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the VA Audie Murphy Hospital in San Antonio, Texas was compared with patients with DLBCL who received R-CHOP in a community setting. According to the researchers, the response to initial treatment was inferior in the veteran population when compared with a patient population with similar demographics and having similar time from diagnosis to treatment. Veteran patients also had worse outcomes when compared with uninsured patients.
This retrospective analysis study identified 2,290 patients with follicular lymphoma treated in the Veterans Health Administration between 2006–2014 and detailed their staging, demographics, and comorbidities. The researchers found that maintenance therapy with rituximab was associated with an improvement in overall survival.
Another retrospective analysis of DBCL using VHA data examined the effectiveness of second-line chemotherapy and chemoimmunotherapy in patients aged ≥ 65 years. The researchers found 230 patients from 2001 to 2015 that met the inclusion criteria. According to the researchers, the overall survival was < 1 year and about half of the patients "did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant."
White Blood Cells
Cost-Effective Use of White Blood Cell Growth Factors in the Veterans Administration
This study analyzed the use of granulocyte colony-stimulating (G-CSF) vs pegfilgrastim in the UD Department of Veterans Affairs (VA) health care system. The researchers looked at the relative frequency of use of filgrastim, Tbo-filgrastim, Filgrastim-sndz and pegfilgrastim at 23 VA sites and found that uptake of biosimilar G-CSF has been extremely rapid. All sites are using biosimilar GCSF for all new patients; 6 of 23 sites were comfortable shifting current patients on branded G-CSF to the biosimilar.However, switching to a Tbo-filgrastim brought a cost savings of 2.2% that was "small compared to other clinical changes."
This analysis described the association between white blood cell (EBC) levels and occurrence of thrombotic events among patients with polycythemia vera (PV) using Veterans Health Administration claims data collected between 2005 and 2012. The researchers found A significant, positive association between increased WBC counts and occurrence of thrombotic events in patients with PV was observed in this study. Patients with WBC counts ≥ 8.5 × 109/L had a significantly increased risk of thrombotic events, and those with counts ≥ 11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of thrombotic events in patients with PV.
Leukemias
Black patients with chronic lymphocytic leukemia tend to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. This retrospective analysis of VHA patients compared black and nonblack patients. It found that black patients had worse survival compared to nonblack patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine.
Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for acute myeloid leukemia (AML) results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Researchers, including former AVAHO president Suman Kambhampati developed a randomized, open-label, controlled Phase 2 trial to study the effect of romyelocel-L in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy.
Multiple Myeloma
Two studies focused on racial disparities in multiple myeloma (MM), while another reported phase 2 data on a relapsed/refractory option.
This group of researchers found an absence of disparity in use of novel agents, no racial disparity was observed in overall survival between black and white patients with MM. Among patients aged < 65 years at diagnosis, the researchers observed a significantly lower age-adjusted risk of death for black patients compared with white patients. The difference in the younger population was not explained by access or utilization of resources. This analysis suggests that when healthcare access is neutralized, younger black patients may even have improved overall survival, which may indicate the possibility of genetic differences that may drive the disease biology and therapeutic outcome in AA patients.
Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration
The second study found survival of black patients with MM was improved compared to non-blacks in the VHA, a national comprehensive care delivery system. Black patients also received similar therapies compared to non-blacks, while presenting at a younger age with more comorbidities. These results are strengthened after adjusting for treatments and patient characteristics not available in other large data studies. Despite increased incidence of MM in the black population, outcomes are improved, similar to other large studies of patients in the United States.
Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a phase 2 study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory MM who have received a first- or second-line treatment of lenalidomide-based therapy. In this trial, researchers (including those from VA facilities, Celgene, and multiple other locations) sought to characterize on-treatment pharmacodynamic changes of immune biomarkers associated with POM + LoDEX + DARA administration (arm B) using multicolor flow cytometry panels designed to characterize T-cell subsets and CD38+ expressing cells. The researchers reported that the triplet regimen POM + LoDEX + DARA has shown notable clinical activity with deep and durable responses in relapsed MM patients progressed and are or refractory to lenalidomide. According to the researchers the results demonstrate that patients treated with the POM + LoDEX + DARA combination do not demonstrate impairment in the innate and adaptive immune compartments and, in contrast, show significant proliferative activity in the subsets of CD4, CD8 and NK cells following treatment.
With hundreds of sessions and thousands of abstracts, it can be difficult to wade through all the new findings to find the most significant and relevant findings. Federal Practitioner consulted with Association of VA Hematology/Oncology members who attended the meeting, VA researchers, and other sources to provide these nuggets you might have missed on lymphomas, white blood cells, leukemias, and multiple myeloma:
Lymphomas
This retrospective analysis of diffuse large B cell lymphoma (DCBL) patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the VA Audie Murphy Hospital in San Antonio, Texas was compared with patients with DLBCL who received R-CHOP in a community setting. According to the researchers, the response to initial treatment was inferior in the veteran population when compared with a patient population with similar demographics and having similar time from diagnosis to treatment. Veteran patients also had worse outcomes when compared with uninsured patients.
This retrospective analysis study identified 2,290 patients with follicular lymphoma treated in the Veterans Health Administration between 2006–2014 and detailed their staging, demographics, and comorbidities. The researchers found that maintenance therapy with rituximab was associated with an improvement in overall survival.
Another retrospective analysis of DBCL using VHA data examined the effectiveness of second-line chemotherapy and chemoimmunotherapy in patients aged ≥ 65 years. The researchers found 230 patients from 2001 to 2015 that met the inclusion criteria. According to the researchers, the overall survival was < 1 year and about half of the patients "did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant."
White Blood Cells
Cost-Effective Use of White Blood Cell Growth Factors in the Veterans Administration
This study analyzed the use of granulocyte colony-stimulating (G-CSF) vs pegfilgrastim in the UD Department of Veterans Affairs (VA) health care system. The researchers looked at the relative frequency of use of filgrastim, Tbo-filgrastim, Filgrastim-sndz and pegfilgrastim at 23 VA sites and found that uptake of biosimilar G-CSF has been extremely rapid. All sites are using biosimilar GCSF for all new patients; 6 of 23 sites were comfortable shifting current patients on branded G-CSF to the biosimilar.However, switching to a Tbo-filgrastim brought a cost savings of 2.2% that was "small compared to other clinical changes."
This analysis described the association between white blood cell (EBC) levels and occurrence of thrombotic events among patients with polycythemia vera (PV) using Veterans Health Administration claims data collected between 2005 and 2012. The researchers found A significant, positive association between increased WBC counts and occurrence of thrombotic events in patients with PV was observed in this study. Patients with WBC counts ≥ 8.5 × 109/L had a significantly increased risk of thrombotic events, and those with counts ≥ 11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of thrombotic events in patients with PV.
Leukemias
Black patients with chronic lymphocytic leukemia tend to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. This retrospective analysis of VHA patients compared black and nonblack patients. It found that black patients had worse survival compared to nonblack patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine.
Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for acute myeloid leukemia (AML) results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Researchers, including former AVAHO president Suman Kambhampati developed a randomized, open-label, controlled Phase 2 trial to study the effect of romyelocel-L in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy.
Multiple Myeloma
Two studies focused on racial disparities in multiple myeloma (MM), while another reported phase 2 data on a relapsed/refractory option.
This group of researchers found an absence of disparity in use of novel agents, no racial disparity was observed in overall survival between black and white patients with MM. Among patients aged < 65 years at diagnosis, the researchers observed a significantly lower age-adjusted risk of death for black patients compared with white patients. The difference in the younger population was not explained by access or utilization of resources. This analysis suggests that when healthcare access is neutralized, younger black patients may even have improved overall survival, which may indicate the possibility of genetic differences that may drive the disease biology and therapeutic outcome in AA patients.
Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration
The second study found survival of black patients with MM was improved compared to non-blacks in the VHA, a national comprehensive care delivery system. Black patients also received similar therapies compared to non-blacks, while presenting at a younger age with more comorbidities. These results are strengthened after adjusting for treatments and patient characteristics not available in other large data studies. Despite increased incidence of MM in the black population, outcomes are improved, similar to other large studies of patients in the United States.
Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a phase 2 study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory MM who have received a first- or second-line treatment of lenalidomide-based therapy. In this trial, researchers (including those from VA facilities, Celgene, and multiple other locations) sought to characterize on-treatment pharmacodynamic changes of immune biomarkers associated with POM + LoDEX + DARA administration (arm B) using multicolor flow cytometry panels designed to characterize T-cell subsets and CD38+ expressing cells. The researchers reported that the triplet regimen POM + LoDEX + DARA has shown notable clinical activity with deep and durable responses in relapsed MM patients progressed and are or refractory to lenalidomide. According to the researchers the results demonstrate that patients treated with the POM + LoDEX + DARA combination do not demonstrate impairment in the innate and adaptive immune compartments and, in contrast, show significant proliferative activity in the subsets of CD4, CD8 and NK cells following treatment.
With hundreds of sessions and thousands of abstracts, it can be difficult to wade through all the new findings to find the most significant and relevant findings. Federal Practitioner consulted with Association of VA Hematology/Oncology members who attended the meeting, VA researchers, and other sources to provide these nuggets you might have missed on lymphomas, white blood cells, leukemias, and multiple myeloma:
Lymphomas
This retrospective analysis of diffuse large B cell lymphoma (DCBL) patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the VA Audie Murphy Hospital in San Antonio, Texas was compared with patients with DLBCL who received R-CHOP in a community setting. According to the researchers, the response to initial treatment was inferior in the veteran population when compared with a patient population with similar demographics and having similar time from diagnosis to treatment. Veteran patients also had worse outcomes when compared with uninsured patients.
This retrospective analysis study identified 2,290 patients with follicular lymphoma treated in the Veterans Health Administration between 2006–2014 and detailed their staging, demographics, and comorbidities. The researchers found that maintenance therapy with rituximab was associated with an improvement in overall survival.
Another retrospective analysis of DBCL using VHA data examined the effectiveness of second-line chemotherapy and chemoimmunotherapy in patients aged ≥ 65 years. The researchers found 230 patients from 2001 to 2015 that met the inclusion criteria. According to the researchers, the overall survival was < 1 year and about half of the patients "did not receive or were not candidates for regimens typically used with intent for high-dose therapy and autologous transplant."
White Blood Cells
Cost-Effective Use of White Blood Cell Growth Factors in the Veterans Administration
This study analyzed the use of granulocyte colony-stimulating (G-CSF) vs pegfilgrastim in the UD Department of Veterans Affairs (VA) health care system. The researchers looked at the relative frequency of use of filgrastim, Tbo-filgrastim, Filgrastim-sndz and pegfilgrastim at 23 VA sites and found that uptake of biosimilar G-CSF has been extremely rapid. All sites are using biosimilar GCSF for all new patients; 6 of 23 sites were comfortable shifting current patients on branded G-CSF to the biosimilar.However, switching to a Tbo-filgrastim brought a cost savings of 2.2% that was "small compared to other clinical changes."
This analysis described the association between white blood cell (EBC) levels and occurrence of thrombotic events among patients with polycythemia vera (PV) using Veterans Health Administration claims data collected between 2005 and 2012. The researchers found A significant, positive association between increased WBC counts and occurrence of thrombotic events in patients with PV was observed in this study. Patients with WBC counts ≥ 8.5 × 109/L had a significantly increased risk of thrombotic events, and those with counts ≥ 11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of thrombotic events in patients with PV.
Leukemias
Black patients with chronic lymphocytic leukemia tend to have worse overall survival and an earlier age at diagnosis with higher rates of adverse cytogenetics. This retrospective analysis of VHA patients compared black and nonblack patients. It found that black patients had worse survival compared to nonblack patients in a single health care delivery system, which limits differences in access to care. Black patients were younger and had shorter periods of observation and were more frequently given first-line fludarabine.
Induction chemotherapy (7+3) or high-dose ara-C-based (HIDAC) for acute myeloid leukemia (AML) results in prolonged neutropenia with a high risk of serious infection and attendant morbidity, and prolonged hospitalization. Researchers, including former AVAHO president Suman Kambhampati developed a randomized, open-label, controlled Phase 2 trial to study the effect of romyelocel-L in de novo patients receiving HIDAC or 7+3 induction therapy for reduction of fever and infection. The results from pooled and 7+3 cohorts, were previously presented, showing decrease in infections and days in hospital. The results from cohorts receiving HIDAC chemotherapy are presented here. The incidence of infections was decreased during the day 15-28 period and a decrease of three days in hospital stay was observed in de novo HIDAC AML subjects receiving romyelocel-L. Romyelocel-L may provide a new option to reduce infections in AML patients undergoing HIDAC induction therapy.
Multiple Myeloma
Two studies focused on racial disparities in multiple myeloma (MM), while another reported phase 2 data on a relapsed/refractory option.
This group of researchers found an absence of disparity in use of novel agents, no racial disparity was observed in overall survival between black and white patients with MM. Among patients aged < 65 years at diagnosis, the researchers observed a significantly lower age-adjusted risk of death for black patients compared with white patients. The difference in the younger population was not explained by access or utilization of resources. This analysis suggests that when healthcare access is neutralized, younger black patients may even have improved overall survival, which may indicate the possibility of genetic differences that may drive the disease biology and therapeutic outcome in AA patients.
Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration
The second study found survival of black patients with MM was improved compared to non-blacks in the VHA, a national comprehensive care delivery system. Black patients also received similar therapies compared to non-blacks, while presenting at a younger age with more comorbidities. These results are strengthened after adjusting for treatments and patient characteristics not available in other large data studies. Despite increased incidence of MM in the black population, outcomes are improved, similar to other large studies of patients in the United States.
Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a phase 2 study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory MM who have received a first- or second-line treatment of lenalidomide-based therapy. In this trial, researchers (including those from VA facilities, Celgene, and multiple other locations) sought to characterize on-treatment pharmacodynamic changes of immune biomarkers associated with POM + LoDEX + DARA administration (arm B) using multicolor flow cytometry panels designed to characterize T-cell subsets and CD38+ expressing cells. The researchers reported that the triplet regimen POM + LoDEX + DARA has shown notable clinical activity with deep and durable responses in relapsed MM patients progressed and are or refractory to lenalidomide. According to the researchers the results demonstrate that patients treated with the POM + LoDEX + DARA combination do not demonstrate impairment in the innate and adaptive immune compartments and, in contrast, show significant proliferative activity in the subsets of CD4, CD8 and NK cells following treatment.
MAIA: Daratumumab plus len-dex improves myeloma PFS
SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.
Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).
The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.
“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.
Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.
In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
MAIA details
The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.
Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.
The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.
The primary endpoint of progression-free survival was superior with DRd.
DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).
The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.
Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.
Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.
Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.
SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.
SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.
Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).
The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.
“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.
Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.
In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
MAIA details
The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.
Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.
The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.
The primary endpoint of progression-free survival was superior with DRd.
DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).
The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.
Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.
Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.
Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.
SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.
SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.
Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).
The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.
“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.
Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.
In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
MAIA details
The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.
Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.
The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.
The primary endpoint of progression-free survival was superior with DRd.
DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).
The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.
Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.
Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.
Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.
SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: At 30 months of follow-up, DRd was associated with a 44% reduction in the risk of death, compared with Rd.
Study details: Randomized phase 3 trial of 737 patients with newly diagnosed multiple myeloma who were ineligible for transplant.
Disclosures: Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.
Source: Facon T et al. ASH 2018, Abstract LBA-2.
Melflufen-dex proves active in multi-resistant MM
SAN DIEGO—The combination of melflufen and dexamethasone demonstrated activity in patients with multi-resistant multiple myeloma (MM) in a phase 2 trial.
Melflufen-dexamethasone produced an overall response rate of 33% in patients who had quad- or penta-refractory MM.
The combination was considered well tolerated, although 13% of patients discontinued treatment due to adverse events (AEs).
Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, presented these results, from the HORIZON trial (NCT02963493), at the 2018 ASH Annual Meeting (abstract 600*).
Dr. Richardson reported results with melflufen-dexamethasone in 83 MM patients. They had a median age of 63 (range, 35-86), and 59% were male. Their median time since diagnosis was 6.5 years (range, 0.7-25) at baseline.
The patients had received a median of 5 prior lines of therapy (range, 2-13). All patients were refractory to pomalidomide or daratumumab, and 60% were refractory to both drugs. Eighty percent of patients were refractory to a monoclonal antibody, and 55% were refractory to an alkylator.
Eighty-six percent of patients were refractory to both a proteasome inhibitor and an immunomodulatory drug. Sixty percent of patients were refractory to a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 therapy.
Ninety-three percent of patients were refractory to their last line of therapy. Sixty-nine percent had received a transplant, and 25% had received two transplants.
“[I]f you look at the refractoriness of these patients, 46% had used three or more prior regimens within the last 12 months before entering the trial, and I think that reflects a real challenge in these patients,” Dr. Richardson said.
Results
The patients received melflufen at 40 mg on day 1 of each 28-day cycle and dexamethasone at 40 mg weekly (20 mg for patients age 75 and older). Patients were treated until progression, consent withdrawal, or unacceptable toxicity.
The overall response rate (partial response or better) was 33%, the clinical benefit rate (minimal response or better) was 39%, and 84% of patients had stable disease or better.
Twenty seven patients responded, including one stringent complete response, nine very good partial responses, and 17 partial responses.
Five patients had a minimal response, 37 had stable disease, and 12 progressed. One patient was not evaluable, and one had data pending.
Dr. Richardson noted that melflufen-dexamethasone demonstrated activity regardless of a patient’s underlying refractory status, but serum albumin was a strong predictor of response. Specifically, patients with higher albumin levels were more likely to respond.
“We do not think it’s a mechanism-of-action issue with [melflufen], but we will be evaluating that,” Dr. Richardson said.
He went on to say that the median progression-free survival was 4.0 months overall, 6.4 months among patients with a partial response or better, and 1 month in patients with progressive disease.
Treatment-related grade 3/4 AEs occurred in 75% of patients. This included neutropenia (61%), thrombocytopenia (59%), anemia (25%), febrile neutropenia (6%), leukopenia (5%), lymphopenia (5%), infections and infestations (7%), and pneumonia (2%).
There were no treatment-related deaths. Thirteen percent of patients discontinued treatment due to AEs, most due to thrombocytopenia (8/11).
In closing, Dr. Richardson said toxicity was “generally manageable” with this treatment, which “has promising activity in multi-resistant, relapsed/refractory myeloma.”
He added that, in the phase 3 OCEAN trial (NCT03151811), researchers are comparing melflufen-dexamethasone to pomalidomide-dexamethasone in a less heavily pretreated MM population.
In the phase 1/2 ANCHOR trial (NCT03481556), researchers are testing melflufen-dexamethasone in combination with daratumumab or bortezomib.
Dr. Richardson disclosed relationships with Karyopharm Pharmaceuticals, Bristol-Myers Squibb, Janssen, Amgen, Jazz Pharmaceuticals, Takeda, Celgene, and Oncopeptides AB. The HORIZON trial is supported by Oncopeptides AB in collaboration with Precision Oncology.
*Data in the abstract differ from the presentation.
SAN DIEGO—The combination of melflufen and dexamethasone demonstrated activity in patients with multi-resistant multiple myeloma (MM) in a phase 2 trial.
Melflufen-dexamethasone produced an overall response rate of 33% in patients who had quad- or penta-refractory MM.
The combination was considered well tolerated, although 13% of patients discontinued treatment due to adverse events (AEs).
Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, presented these results, from the HORIZON trial (NCT02963493), at the 2018 ASH Annual Meeting (abstract 600*).
Dr. Richardson reported results with melflufen-dexamethasone in 83 MM patients. They had a median age of 63 (range, 35-86), and 59% were male. Their median time since diagnosis was 6.5 years (range, 0.7-25) at baseline.
The patients had received a median of 5 prior lines of therapy (range, 2-13). All patients were refractory to pomalidomide or daratumumab, and 60% were refractory to both drugs. Eighty percent of patients were refractory to a monoclonal antibody, and 55% were refractory to an alkylator.
Eighty-six percent of patients were refractory to both a proteasome inhibitor and an immunomodulatory drug. Sixty percent of patients were refractory to a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 therapy.
Ninety-three percent of patients were refractory to their last line of therapy. Sixty-nine percent had received a transplant, and 25% had received two transplants.
“[I]f you look at the refractoriness of these patients, 46% had used three or more prior regimens within the last 12 months before entering the trial, and I think that reflects a real challenge in these patients,” Dr. Richardson said.
Results
The patients received melflufen at 40 mg on day 1 of each 28-day cycle and dexamethasone at 40 mg weekly (20 mg for patients age 75 and older). Patients were treated until progression, consent withdrawal, or unacceptable toxicity.
The overall response rate (partial response or better) was 33%, the clinical benefit rate (minimal response or better) was 39%, and 84% of patients had stable disease or better.
Twenty seven patients responded, including one stringent complete response, nine very good partial responses, and 17 partial responses.
Five patients had a minimal response, 37 had stable disease, and 12 progressed. One patient was not evaluable, and one had data pending.
Dr. Richardson noted that melflufen-dexamethasone demonstrated activity regardless of a patient’s underlying refractory status, but serum albumin was a strong predictor of response. Specifically, patients with higher albumin levels were more likely to respond.
“We do not think it’s a mechanism-of-action issue with [melflufen], but we will be evaluating that,” Dr. Richardson said.
He went on to say that the median progression-free survival was 4.0 months overall, 6.4 months among patients with a partial response or better, and 1 month in patients with progressive disease.
Treatment-related grade 3/4 AEs occurred in 75% of patients. This included neutropenia (61%), thrombocytopenia (59%), anemia (25%), febrile neutropenia (6%), leukopenia (5%), lymphopenia (5%), infections and infestations (7%), and pneumonia (2%).
There were no treatment-related deaths. Thirteen percent of patients discontinued treatment due to AEs, most due to thrombocytopenia (8/11).
In closing, Dr. Richardson said toxicity was “generally manageable” with this treatment, which “has promising activity in multi-resistant, relapsed/refractory myeloma.”
He added that, in the phase 3 OCEAN trial (NCT03151811), researchers are comparing melflufen-dexamethasone to pomalidomide-dexamethasone in a less heavily pretreated MM population.
In the phase 1/2 ANCHOR trial (NCT03481556), researchers are testing melflufen-dexamethasone in combination with daratumumab or bortezomib.
Dr. Richardson disclosed relationships with Karyopharm Pharmaceuticals, Bristol-Myers Squibb, Janssen, Amgen, Jazz Pharmaceuticals, Takeda, Celgene, and Oncopeptides AB. The HORIZON trial is supported by Oncopeptides AB in collaboration with Precision Oncology.
*Data in the abstract differ from the presentation.
SAN DIEGO—The combination of melflufen and dexamethasone demonstrated activity in patients with multi-resistant multiple myeloma (MM) in a phase 2 trial.
Melflufen-dexamethasone produced an overall response rate of 33% in patients who had quad- or penta-refractory MM.
The combination was considered well tolerated, although 13% of patients discontinued treatment due to adverse events (AEs).
Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, presented these results, from the HORIZON trial (NCT02963493), at the 2018 ASH Annual Meeting (abstract 600*).
Dr. Richardson reported results with melflufen-dexamethasone in 83 MM patients. They had a median age of 63 (range, 35-86), and 59% were male. Their median time since diagnosis was 6.5 years (range, 0.7-25) at baseline.
The patients had received a median of 5 prior lines of therapy (range, 2-13). All patients were refractory to pomalidomide or daratumumab, and 60% were refractory to both drugs. Eighty percent of patients were refractory to a monoclonal antibody, and 55% were refractory to an alkylator.
Eighty-six percent of patients were refractory to both a proteasome inhibitor and an immunomodulatory drug. Sixty percent of patients were refractory to a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 therapy.
Ninety-three percent of patients were refractory to their last line of therapy. Sixty-nine percent had received a transplant, and 25% had received two transplants.
“[I]f you look at the refractoriness of these patients, 46% had used three or more prior regimens within the last 12 months before entering the trial, and I think that reflects a real challenge in these patients,” Dr. Richardson said.
Results
The patients received melflufen at 40 mg on day 1 of each 28-day cycle and dexamethasone at 40 mg weekly (20 mg for patients age 75 and older). Patients were treated until progression, consent withdrawal, or unacceptable toxicity.
The overall response rate (partial response or better) was 33%, the clinical benefit rate (minimal response or better) was 39%, and 84% of patients had stable disease or better.
Twenty seven patients responded, including one stringent complete response, nine very good partial responses, and 17 partial responses.
Five patients had a minimal response, 37 had stable disease, and 12 progressed. One patient was not evaluable, and one had data pending.
Dr. Richardson noted that melflufen-dexamethasone demonstrated activity regardless of a patient’s underlying refractory status, but serum albumin was a strong predictor of response. Specifically, patients with higher albumin levels were more likely to respond.
“We do not think it’s a mechanism-of-action issue with [melflufen], but we will be evaluating that,” Dr. Richardson said.
He went on to say that the median progression-free survival was 4.0 months overall, 6.4 months among patients with a partial response or better, and 1 month in patients with progressive disease.
Treatment-related grade 3/4 AEs occurred in 75% of patients. This included neutropenia (61%), thrombocytopenia (59%), anemia (25%), febrile neutropenia (6%), leukopenia (5%), lymphopenia (5%), infections and infestations (7%), and pneumonia (2%).
There were no treatment-related deaths. Thirteen percent of patients discontinued treatment due to AEs, most due to thrombocytopenia (8/11).
In closing, Dr. Richardson said toxicity was “generally manageable” with this treatment, which “has promising activity in multi-resistant, relapsed/refractory myeloma.”
He added that, in the phase 3 OCEAN trial (NCT03151811), researchers are comparing melflufen-dexamethasone to pomalidomide-dexamethasone in a less heavily pretreated MM population.
In the phase 1/2 ANCHOR trial (NCT03481556), researchers are testing melflufen-dexamethasone in combination with daratumumab or bortezomib.
Dr. Richardson disclosed relationships with Karyopharm Pharmaceuticals, Bristol-Myers Squibb, Janssen, Amgen, Jazz Pharmaceuticals, Takeda, Celgene, and Oncopeptides AB. The HORIZON trial is supported by Oncopeptides AB in collaboration with Precision Oncology.
*Data in the abstract differ from the presentation.
Tom Brokaw opens up on surviving multiple myeloma
SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.
“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”
Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”
Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.
In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.
In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”
“There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”
At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”
He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”
“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.
Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”
SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.
“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”
Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”
Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.
In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.
In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”
“There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”
At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”
He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”
“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.
Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”
SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.
“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”
Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”
Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.
In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.
In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”
“There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”
At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”
He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”
“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.
Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”
EXPERT ANALYSIS FROM ASH 2018
Triplet demonstrates activity in relapsed/refractory MM
SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.
Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.
The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.
Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*
Patients
As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).
Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.
All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.
Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.
Treatment
Patients were treated in two concurrent cohorts.
One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.
The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
Safety
Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:
- Nausea (60%)
- Diarrhea (32%)
- Anorexia (28%)
- Vomiting (24%)
- Dysgeusia (20%)
- Fatigue (48%)
- Hyponatremia (28%)
- Insomnia (24%)
- Blurred vision (24%)
- Thrombocytopenia (64%)
- Anemia (48%)
- Leukopenia (44%)
- Neutropenia (44%)
- Lymphopenia (20%).
“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.
The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.
Efficacy
The median follow-up was 7.7 months, and the median time on study was 5.8 months.
Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.
The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.
Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.
Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.
Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).
One patient with a minimal response progressed, and one discontinued treatment due to an AE.
The median progression-free survival was not reached.
“Selinexor in combination with dara and dexa appears to be highly active, producing deep and durable responses in the relapsed setting,” Dr. Gasparetto said.
She reported relationships with Takeda, Janssen, Celgene, and Bristol-Myers Squibb. The trial is sponsored by Karyopharm Therapeutics.
*Data in the presentation differ from the abstract.
SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.
Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.
The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.
Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*
Patients
As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).
Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.
All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.
Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.
Treatment
Patients were treated in two concurrent cohorts.
One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.
The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
Safety
Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:
- Nausea (60%)
- Diarrhea (32%)
- Anorexia (28%)
- Vomiting (24%)
- Dysgeusia (20%)
- Fatigue (48%)
- Hyponatremia (28%)
- Insomnia (24%)
- Blurred vision (24%)
- Thrombocytopenia (64%)
- Anemia (48%)
- Leukopenia (44%)
- Neutropenia (44%)
- Lymphopenia (20%).
“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.
The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.
Efficacy
The median follow-up was 7.7 months, and the median time on study was 5.8 months.
Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.
The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.
Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.
Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.
Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).
One patient with a minimal response progressed, and one discontinued treatment due to an AE.
The median progression-free survival was not reached.
“Selinexor in combination with dara and dexa appears to be highly active, producing deep and durable responses in the relapsed setting,” Dr. Gasparetto said.
She reported relationships with Takeda, Janssen, Celgene, and Bristol-Myers Squibb. The trial is sponsored by Karyopharm Therapeutics.
*Data in the presentation differ from the abstract.
SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.
Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.
The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.
Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*
Patients
As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).
Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.
All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.
Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.
Treatment
Patients were treated in two concurrent cohorts.
One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.
The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
Safety
Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:
- Nausea (60%)
- Diarrhea (32%)
- Anorexia (28%)
- Vomiting (24%)
- Dysgeusia (20%)
- Fatigue (48%)
- Hyponatremia (28%)
- Insomnia (24%)
- Blurred vision (24%)
- Thrombocytopenia (64%)
- Anemia (48%)
- Leukopenia (44%)
- Neutropenia (44%)
- Lymphopenia (20%).
“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.
The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.
Efficacy
The median follow-up was 7.7 months, and the median time on study was 5.8 months.
Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.
The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.
Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.
Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.
Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).
One patient with a minimal response progressed, and one discontinued treatment due to an AE.
The median progression-free survival was not reached.
“Selinexor in combination with dara and dexa appears to be highly active, producing deep and durable responses in the relapsed setting,” Dr. Gasparetto said.
She reported relationships with Takeda, Janssen, Celgene, and Bristol-Myers Squibb. The trial is sponsored by Karyopharm Therapeutics.
*Data in the presentation differ from the abstract.
LCAR-B38M CAR T therapy appears durable in myeloma
SAN DIEGO – The chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M is in the race for approval in multiple myeloma following encouraging phase 1 results reported at the annual meeting of the American Society of Hematology.
In the LEGEND-2 phase 1/2 open study of 57 patients with advanced relapsed/refractory multiple myeloma treated with the investigational CAR T therapy, the overall response rate was 88% and the complete response rate was 74%. Among 42 patients who achieved complete response, 39 (68%) were negative for minimal residual disease (MRD).
With a median follow-up of 12 months, the median duration of response was 16 months and progression-free survival was 15 months. But in patients who achieved MRD-negative complete response, the median progression-free survival was extended to 24 months.
Pyrexia and cytokine release syndrome were reported in 90% or more of patients. Thrombocytopenia and leukopenia were reported in nearly half of patients.
The phase 1 study was conducted by researchers from the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. The B-cell maturation antigen (BCMA)–directed CAR T-cell therapy is being jointly developed by Nanjing Legend Biotech and Janssen. A phase 2 study is currently being planned in China for LCAR-B38M. In parallel, Janssen and Legend are enrolling patients in a phase 1b/2 trial of the agent (also known as JNJ-68284528) in the United States.
The therapy joins a growing field of anti-BCMA CAR T-cell agents with promising initial trial results, including bb2121.
In a video interview at ASH, Sen Zhuang, MD, PhD, vice president of oncology clinical development at Janssen Research & Development, said this class of CAR T agents offers the potential for “very long remissions” and possibly even a “cure” for myeloma.
The LEGEND-2 study is sponsored by Nanjing Legend Biotech and two of the investigators reported employment with the company.
SAN DIEGO – The chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M is in the race for approval in multiple myeloma following encouraging phase 1 results reported at the annual meeting of the American Society of Hematology.
In the LEGEND-2 phase 1/2 open study of 57 patients with advanced relapsed/refractory multiple myeloma treated with the investigational CAR T therapy, the overall response rate was 88% and the complete response rate was 74%. Among 42 patients who achieved complete response, 39 (68%) were negative for minimal residual disease (MRD).
With a median follow-up of 12 months, the median duration of response was 16 months and progression-free survival was 15 months. But in patients who achieved MRD-negative complete response, the median progression-free survival was extended to 24 months.
Pyrexia and cytokine release syndrome were reported in 90% or more of patients. Thrombocytopenia and leukopenia were reported in nearly half of patients.
The phase 1 study was conducted by researchers from the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. The B-cell maturation antigen (BCMA)–directed CAR T-cell therapy is being jointly developed by Nanjing Legend Biotech and Janssen. A phase 2 study is currently being planned in China for LCAR-B38M. In parallel, Janssen and Legend are enrolling patients in a phase 1b/2 trial of the agent (also known as JNJ-68284528) in the United States.
The therapy joins a growing field of anti-BCMA CAR T-cell agents with promising initial trial results, including bb2121.
In a video interview at ASH, Sen Zhuang, MD, PhD, vice president of oncology clinical development at Janssen Research & Development, said this class of CAR T agents offers the potential for “very long remissions” and possibly even a “cure” for myeloma.
The LEGEND-2 study is sponsored by Nanjing Legend Biotech and two of the investigators reported employment with the company.
SAN DIEGO – The chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M is in the race for approval in multiple myeloma following encouraging phase 1 results reported at the annual meeting of the American Society of Hematology.
In the LEGEND-2 phase 1/2 open study of 57 patients with advanced relapsed/refractory multiple myeloma treated with the investigational CAR T therapy, the overall response rate was 88% and the complete response rate was 74%. Among 42 patients who achieved complete response, 39 (68%) were negative for minimal residual disease (MRD).
With a median follow-up of 12 months, the median duration of response was 16 months and progression-free survival was 15 months. But in patients who achieved MRD-negative complete response, the median progression-free survival was extended to 24 months.
Pyrexia and cytokine release syndrome were reported in 90% or more of patients. Thrombocytopenia and leukopenia were reported in nearly half of patients.
The phase 1 study was conducted by researchers from the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. The B-cell maturation antigen (BCMA)–directed CAR T-cell therapy is being jointly developed by Nanjing Legend Biotech and Janssen. A phase 2 study is currently being planned in China for LCAR-B38M. In parallel, Janssen and Legend are enrolling patients in a phase 1b/2 trial of the agent (also known as JNJ-68284528) in the United States.
The therapy joins a growing field of anti-BCMA CAR T-cell agents with promising initial trial results, including bb2121.
In a video interview at ASH, Sen Zhuang, MD, PhD, vice president of oncology clinical development at Janssen Research & Development, said this class of CAR T agents offers the potential for “very long remissions” and possibly even a “cure” for myeloma.
The LEGEND-2 study is sponsored by Nanjing Legend Biotech and two of the investigators reported employment with the company.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: The complete response rate was 74% with median progression-free survival of 15 months.
Study details: A phase 1/2 study of 57 patients with advanced relapsed/refractory multiple myeloma.
Disclosures: The study is sponsored by Nanjing Legend Biotech. Two of the investigators reported employment with the company.
Ixazomib improves PFS after ASCT in MM
SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.
The oral proteasome inhibitor improved PFS by 39% compared to placebo.
In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.
TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.
Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).
He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.
“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.
He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.
The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.
The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).
At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.
The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.
Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.
When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”
However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.
“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.
A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.
TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.
Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene.
SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.
The oral proteasome inhibitor improved PFS by 39% compared to placebo.
In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.
TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.
Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).
He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.
“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.
He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.
The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.
The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).
At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.
The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.
Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.
When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”
However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.
“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.
A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.
TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.
Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene.
SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.
The oral proteasome inhibitor improved PFS by 39% compared to placebo.
In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.
TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.
Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).
He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.
“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.
He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.
The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.
The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).
At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.
The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.
Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.
When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”
However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.
“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.
A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.
TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.
Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene.
